Abstract 2170: Pre-treatment protein landscape in HER2-negative breast cancer treated with carboplatin in a neoadjuvant chemotherapy setting
Authors: Maria Aanesland Dahle, Eivind Valen Egeland, Lina Prasmickaite, Ole Christian Lingjærde, Hege Russnes, Øystein Garred, Marianne L. Smebye, Helle Skjerven, Ellen Schlichting, Bjørn Naume, Gunhild Mælandsmo, Olav Engebraaten, Mads H. Haugen
Journal: Cancer Research (2023)

Abstract Background and Purpose: Neoadjuvant treatment regimens containing the DNA-targeting chemotherapy carboplatin has been shown to increase the pathological complete response (pCR) rate in triple negative (TN) breast cancer. In addition, the response to such therapy among patients with aggressive hormone receptor positive (HR+) cancer should be investigated. Neither the molecular mechanisms leading to good response, nor the criteria for selection of optimal treatment groups are known. Therefore, predictive biomarkers that identify responders to carboplatin in breast cancer are needed. Materials and Methods: In the I-BCT phase II clinical trial (ClinicalTrials.gov identifier: NCT02546232), HER2-negative breast cancer patients (N = 187) were randomized (1:1) to receive neoadjuvant chemotherapy with or without carboplatin. Pre-treatment tumor biopsies (N = 178, N = 89 in each arm) were analyzed by reverse-phase protein array (RPPA) for expression levels of 494 breast cancer relevant (phospho-) proteins. Change in tumor size during treatment was used as continuous response measure. In addition, response was dichotomized with 30 % tumor shrinkage as cutoff. For the patients that received carboplatin, differential expression analysis between responders and non-responders was performed to identify proteins that may predict response to carboplatin. Gene set enrichment analysis on differentially expressed proteins was performed to identify biologically upregulated pathways. Results: We found differentially expressed proteins related to response to carboplatin in treatment naive tumors. Biologically upregulated pathways have been identified in patients with high tumor shrinkage after treatment with carboplatin. The results demonstrate the importance of the pre-treatment protein landscape in prediction of benefit to carboplatin. Studies regarding biological mechanisms related to response in both TN and HR+ breast cancer, and differences among these subtypes, are ongoing. Conclusion: Our study provides new insight into the mechanisms of response and resistance to carboplatin treatment in the neoadjuvant setting for HER2-negative breast cancer patients. The results support further studies on the protein landscape of tumors as a complementary method to gene expression analysis to unravel the molecular mechanisms of sensitivity and resistance to treatment in breast cancer. Citation Format: Maria Aanesland Dahle, Eivind Valen Egeland, Lina Prasmickaite, Ole Christian Lingjærde, Hege Russnes, Øystein Garred, Marianne L. Smebye, Helle Skjerven, Ellen Schlichting, Bjørn Naume, Gunhild Mælandsmo, Olav Engebraaten, Mads H. Haugen. Pre-treatment protein landscape in HER2-negative breast cancer treated with carboplatin in a neoadjuvant chemotherapy setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2170.